This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A naturally occurring 8R-lipoxygenase (8R-LOX) and allene oxide synthase fusion (AOS) protein from Plexaura homomalla catalyses successive steps in a biosynthetic pathway. The intermediate in the reaction, the 8R-hydroperoxy derivative of arachidonic acid, is both hydrophobic and labile. In order to understand how an assembly of catalytic activities impacts the transfer of the reaction intermediate, and thus the efficiency of biosynthesis, we will determine the structure of the lipoxygenase-allene oxide synthase complex. We have determined the crystal structures of the independently expressed domains, and have shown that they associate into a heterodimer. In addition we have shown that Ca2+ binding promotes membrane binding of the lipoxygenase domain. Experiments to elucidate conformational changes that occur (1) during the catalytic cycle and (2) upon Ca2+ binding are also proposed.